ArticleMolecular biology of the cell2003
Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Network analysis identifies a gene biomarker panel for sepsis-induced acute respiratory distress syndrome.BMC medical genomics · 2023Article
- Defining a role for lung function associated gene GSTCD in cell homeostasis.Respiratory research · 2019Article
- Betaine in Inflammation: Mechanistic Aspects and Applications.Frontiers in immunology · 2018Review
- Pulmonary Endothelial Cell Apoptosis in Emphysema and Acute Lung Injury.Advances in anatomy, embryology, and cell biology · 2018Review
- Isoprenyl carboxyl methyltransferase inhibitors: a brief review including recent patents.Amino acids · 2017Review
- Occupancy of human EPCR by protein C induces β-arrestin-2 biased PAR1 signaling by both APC and thrombin.Blood · 2016Article
- Non-Substrate Based, Small Molecule Inhibitors of the Human Isoprenylcysteine Carboxyl Methyltransferase.MedChemComm · 2016Article
- Focal adhesion kinase and endothelial cell apoptosis.Microvascular research · 2012Review
- RAS-converting enzyme 1-mediated endoproteolysis is required for trafficking of rod phosphodiesterase 6 to photoreceptor outer segments.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Involvement and mechanism of DGAT2 upregulation in the pathogenesis of alcoholic fatty liver disease.Journal of lipid research · 2010Article
- Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth.Oncogene · 2010Article
- Biochemical and docking analysis of substrate interactions with polyisoprenylated methylated protein methyl esterase.Current cancer drug targets · 2010Review
- Clostridium difficile toxin B differentially affects GPCR-stimulated Ca2+ responses in macrophages: independent roles for Rho and PLA2.Journal of leukocyte biology · 2010Article
- Alterations in molecular chaperones and eIF2alpha during lung endothelial cell apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2010Article
- Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5.American journal of physiology. Lung cellular and molecular physiology · 2008Article
- Pulmonary endothelial cell signaling and function.Transactions of the American Clinical and Climatological Association · 2008Article
- Role of transmethylation reactions in alcoholic liver disease.World journal of gastroenterology · 2007Review
- Inhibition of ICMT induces endothelial cell apoptosis through GRP94.American journal of respiratory cell and molecular biology · 2007Article
- Mining literature for a comprehensive pathway analysis: a case study for retrieval of homocysteine related genes for genetic and epigenetic studies.Lipids in health and disease · 2006Review
- A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular ATP, adenosine (Ado), and adenosine plus homocysteine (Ado/HC) cause apoptosis of cultured pulmonary artery endothelial cells through the enhanced formation of intracellular S-adenosylhomocysteine and disruption of focal adhesion complexes. Because an increased intracellular ratio of S-adenosylhomocysteine/S-adenosylmethionine favors inhibition of methylation, we hypothesized that Ado/HC might act by inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT). We found that N-acetyl-S-geranylgeranyl-L-cysteine (AGGC) and N-acetyl-S-farnesyl-L-cysteine (AFC), which inhibit ICMT by competing with endogenous substrates for methylation, caused apoptosis. Transient overexpression of ICMT inhibited apoptosis caused by Ado/HC, UV light exposure, or tumor necrosis factor-alpha. Because the small GTPase, Ras, is a substrate for ICMT and may modulate apoptosis, we also hypothesized that inhibition of ICMT with Ado/HC or AGGC might cause endothelial apoptosis by altering Ras activation. We found that ICMT inhibition decreased Ras methylation and activity and the activation of the downstream signaling molecules Akt, ERK-1, and ERK-2. Furthermore, overexpression of wild-type or dominant active H-Ras blocked Ado/HC-induced apoptosis. These findings suggest that inhibition of ICMT causes endothelial cell apoptosis by attenuation of Ras GTPase methylation and activation and its downstream antiapoptotic signaling pathway.
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